This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hollow gold nanospheres (HAuNS) possess a unique combination of small size (~40 nm), spherical shape, hollow interior, and strong surface plasmon resonance at near-infrared (NIR) region wavelengths (~800 nm), wherein optical absorption in tissue is minimal and penetration is optimal. We propose to develop a multi-modulated nanotechnology which could be applied to concurrent photothermal therapy and chemotherapy of melanoma. This technology is based on the formulation of cisplatin-loaded HAuNS, where a small peptide, Ac-Glu-Glu-Cys-NH2 (EEC), is designed to serve as both cisplatin coordinator and linker to gold nanoparticles. [Nle4,D-Phe7] alpha[unreadable]melanocyte-stimulating hormone (NDP-MSH) peptide will be conjugated on the particles as melanoma homing moiety. Through intravenous administration, dual modulation of the drug-loaded nanoparticle will be investigated. First, the particles are expected to have tumor targeting effect and sustained release properties promoting superior anticancer effect and decreased toxicity. Second, upon NIR laser modulation, the combination of photothermal therapy with HAuNS and chemotherapy with laser-controlled drug release may produce a synergistic anticancer effect to overcome tumor regrowth and cisplatin resistance. The success of this technique will be viewed as a paradigm in the treatment of accessible recurrent neoplasms and lead to more effective and patient-compliant treatment over exisitng treatment protocols. This technology may be further explored for application to other cancers and has the potential to produce a major impact in cancer-relevant research.